This is the second and final revision of a research grant to characterize nicotine withdrawal in pregnant smokers. Maternal cigarette smoking is the leading preventable cause of poor pregnancy outcomes and pediatric morbidity and mortality in the U.S. While 80% of pregnant cigarette smokers report seriously thinking about quitting while pregnant, most are unable to quit for even one week. Efficacious interventions have been developed for smoking cessation during pregnancy, but cessation rates are low, typically under 20%. One factor thought to play a substantial role in early smoking relapse and extensively investigated in non- pregnant smokers is nicotine withdrawal. To our knowledge, there are only two reports on nicotine withdrawal during pregnancy: a retrospective study in pregnant adolescents by Albrecht and colleagues (1999) and our group's recent prospective pilot study (Heil et al., 2006). Given nearly 30 years of research on smoking cessation during pregnancy, this represents a striking gap in this literature. Our initial pilot study resulted in two seminal findings. First, we observed that pregnant smokers report substantially elevated levels of withdrawal symptomatology prior to the cessation attempt. Second, even with this pre-cessation elevation, we were able to validate a number of withdrawal symptoms in pregnant smokers who sustained abstinence for five days and establish their incidence, magnitude, and acute time course. While a significant step forward, our pilot study raised additional questions about nicotine withdrawal symptomatology in pregnant smokers. The two aims that make up the proposed study are designed to follow up and extend the literature in this area. First, we propose performing a thorough examination of pre- cessation elevated withdrawal symptomatology, comparing levels in pregnant smokers to those in pregnant non-smokers and non-pregnant female smokers in an effort to elucidate the source of the increased symptomatology. Second, we propose performing a more comprehensive and rigorous characterization of nicotine withdrawal during pregnancy, increasing the sample size and lengthening the time course from our pilot study. The proposed study will partner with an ongoing clinical trial testing the efficacy of voucher-based incentives to promote smoking cessation during pregnancy. We will analyze nicotine withdrawal data collected from pregnant women who abstain as part of this trial and compare results to those of abstinent non-pregnant female smokers and pregnant non-smokers. PUBLIC HEALTH RELEVANCE: The proposed study has the potential to contribute important new information about nicotine withdrawal among pregnant women. Such new knowledge may contribute to the development of more effective treatments for one of our nation's most daunting drug abuse problems. [unreadable] [unreadable] [unreadable]